Abstract Cryptosporidium is a protozoan parasite that causes diarrheal disease (cryptosporidiosis) and deaths in young children, and immunocompromised individuals such as HIV/AIDS patients and transplant recipients. Recent global epidemiological studies report that Cryptosporidium is the second leading pathogen after rotavirus to cause life-threatening diarrhea in infants and toddlers. Recurrent episodes of Cryptosporidium infection are associated with chronic malnutrition, growth stunting and impaired cognitive development in young children. The infection occurs through ingestion of water and food contaminated with oocysts. Since these ?spore-like? oocysts are resistant to standard disinfection procedures, waterborne outbreaks are very common and reported worldwide. Infact, Cryptosporidium is responsible for 50% of disease outbreaks linked to recreational water use in the US. There are no effective drugs or vaccines to treat or prevent cryptosporidiosis. The only FDA approved drug, Nitazoxanide provides little to no relief to young children or HIV/AIDS patients that need it the most. Therefore, there is an urgent need to develop new drugs and vaccines to reduce the burden of cryptosporidiosis. To discover novel therapeutics, it is crucial to dissect Cryptosporidum biology and identify its ?Achilles heel?. Currently, there is very limited understanding of parasite biology due to lack of methods to continuously culture Cryptosporidum in the laboratory, poor animal models, and lack of molecular tools to genetically modify this pathogen. Recently, we have developed a robust technology to genetically manipulate C. parvum, and an animal infection model to propagate these parasites, thus providing an exciting opportunity to answer fundamental questions regarding parasite biology, virulence and disease pathogenesis. Despite these advances, we are still lacking tools to study genes essential for parasite survival, since deleting these genes would be lethal to the parasite. Thus, the goal of this project is to apply our expertise in molecular genetics and develop a powerful conditional protein degradation tool to unravel the function of essential genes in Cryptosporidium. Elucidation of the function of essential genes throughout the parasite lifecycle would ultimately lead to the development of novel drugs and vaccines to treat cryptosporidiosis.